Genetic Variant NM_000504.4:c.792C>T (chr13-113147423-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000504.4(F10):c.792C>T(p.Thr264Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 1,612,706 control chromosomes in the GnomAD database, including 552,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 42074 hom., cov: 31)

Exomes 𝑓: 0.83 ( 510602 hom. )

Consequence

F10
NM_000504.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.404

Publications

32 publications found

Variant links:

Genes affected

F10 (HGNC:3528): (coagulation factor X) This gene encodes the vitamin K-dependent coagulation factor X of the blood coagulation cascade. This factor undergoes multiple processing steps before its preproprotein is converted to a mature two-chain form by the excision of the tripeptide RKR. Two chains of the factor are held together by 1 or more disulfide bonds; the light chain contains 2 EGF-like domains, while the heavy chain contains the catalytic domain which is structurally homologous to those of the other hemostatic serine proteases. The mature factor is activated by the cleavage of the activation peptide by factor IXa (in the intrisic pathway), or by factor VIIa (in the extrinsic pathway). The activated factor then converts prothrombin to thrombin in the presence of factor Va, Ca+2, and phospholipid during blood clotting. Mutations of this gene result in factor X deficiency, a hemorrhagic condition of variable severity. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides. [provided by RefSeq, Aug 2015]

F10 Gene-Disease associations (from GenCC):

congenital factor X deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

F10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 13-113147423-C-T is Benign according to our data. Variant chr13-113147423-C-T is described in ClinVar as Benign. ClinVar VariationId is 256308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.404 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000504.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
F10	NM_000504.4	MANE Select	c.792C>T	p.Thr264Thr	synonymous	Exon 7 of 8	NP_000495.1	Q5JVE7
F10	NM_001312674.2		c.660C>T	p.Thr220Thr	synonymous	Exon 6 of 7	NP_001299603.1
F10	NM_001312675.2		c.792C>T	p.Thr264Thr	synonymous	Exon 7 of 8	NP_001299604.1	Q5JVE8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
F10	ENST00000375559.8	TSL:1 MANE Select	c.792C>T	p.Thr264Thr	synonymous	Exon 7 of 8	ENSP00000364709.3	P00742
F10	ENST00000375551.7	TSL:1	c.792C>T	p.Thr264Thr	synonymous	Exon 7 of 8	ENSP00000364701.3	Q5JVE8
F10	ENST00000410083.6	TSL:1	n.*751C>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000386320.2	F8WBM7

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110222

AN:

151928

Hom.:

42077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.942

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.882

Gnomad EAS

AF:

0.510

Gnomad SAS

AF:

0.704

Gnomad FIN

AF:

0.819

Gnomad MID

AF:

0.825

Gnomad NFE

AF:

0.862

Gnomad OTH

AF:

0.744

GnomAD2 exomes

AF:

0.758

AC:

190425

AN:

251204

AF XY:

0.769

show subpopulations

Gnomad AFR exome

AF:

0.488

Gnomad AMR exome

AF:

0.634

Gnomad ASJ exome

AF:

0.888

Gnomad EAS exome

AF:

0.492

Gnomad FIN exome

AF:

0.825

Gnomad NFE exome

AF:

0.864

Gnomad OTH exome

AF:

0.795

GnomAD4 exome

AF:

0.831

AC:

1213187

AN:

1460660

Hom.:

510602

Cov.:

AF XY:

0.829

AC XY:

602435

AN XY:

726676

show subpopulations

African (AFR)

AF:

0.485

AC:

16209

AN:

33442

American (AMR)

AF:

0.643

AC:

28727

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.884

AC:

23080

AN:

26116

East Asian (EAS)

AF:

0.546

AC:

21677

AN:

39682

South Asian (SAS)

AF:

0.713

AC:

61450

AN:

86216

European-Finnish (FIN)

AF:

0.826

AC:

44083

AN:

53398

Middle Eastern (MID)

AF:

0.855

AC:

4928

AN:

5762

European-Non Finnish (NFE)

AF:

0.868

AC:

964690

AN:

1110986

Other (OTH)

AF:

0.801

AC:

48343

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

10013

20025

30038

40050

50063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21058

42116

63174

84232

105290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.725

AC:

110246

AN:

152046

Hom.:

42074

Cov.:

AF XY:

0.720

AC XY:

53520

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.495

AC:

20484

AN:

41416

American (AMR)

AF:

0.702

AC:

10734

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.882

AC:

3064

AN:

3472

East Asian (EAS)

AF:

0.510

AC:

2627

AN:

5152

South Asian (SAS)

AF:

0.704

AC:

3388

AN:

4814

European-Finnish (FIN)

AF:

0.819

AC:

8674

AN:

10596

Middle Eastern (MID)

AF:

0.825

AC:

241

AN:

292

European-Non Finnish (NFE)

AF:

0.862

AC:

58611

AN:

67998

Other (OTH)

AF:

0.741

AC:

1566

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1370

2739

4109

5478

6848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.815

Hom.:

204964

Bravo

AF:

0.708

Asia WGS

AF:

0.572

AC:

1994

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Hereditary factor X deficiency disease (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.3

(source)

DANN

Benign

0.33

PhyloP100

-0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over